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NM_000179.3(MSH6):c.3439-26_3439-25del AND not specified

Germline classification:
Benign/Likely benign (2 submissions)
Last evaluated:
Aug 15, 2023
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV001192492.5

Allele description [Variation Report for NM_000179.3(MSH6):c.3439-26_3439-25del]

NM_000179.3(MSH6):c.3439-26_3439-25del

Gene:
MSH6:mutS homolog 6 [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
2p16.3
Genomic location:
Preferred name:
NM_000179.3(MSH6):c.3439-26_3439-25del
HGVS:
  • NC_000002.12:g.47804884_47804885del
  • NG_007111.1:g.26738_26739del
  • NM_000179.3:c.3439-26_3439-25delMANE SELECT
  • NM_001281492.2:c.3049-26_3049-25del
  • NM_001281493.2:c.2533-26_2533-25del
  • NM_001281494.2:c.2533-26_2533-25del
  • LRG_219t1:c.3439-26_3439-25del
  • LRG_219:g.26738_26739del
  • NC_000002.11:g.48032023_48032024del
  • NM_000179.2:c.3439-26_3439-25del
  • NM_000179.3:c.3439-26_3439-25delAAMANE SELECT
Links:
dbSNP: rs750310368
NCBI 1000 Genomes Browser:
rs750310368
Molecular consequence:
  • NM_000179.3:c.3439-26_3439-25del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001281492.2:c.3049-26_3049-25del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001281493.2:c.2533-26_2533-25del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001281494.2:c.2533-26_2533-25del - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001360649Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Benign
(Dec 12, 2019) 		germlineclinical testing

Citation Link,

SCV002552342Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital
criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely benign
(Aug 15, 2023) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001360649.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

Variant summary: MSH6 c.3439-26_3439-25delAA is located at a position not widely known to affect splicing. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 9.1e-05 in 251388 control chromosomes, predominantly at a frequency of 0.00074 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 5.21 fold of the estimated maximal expected allele frequency for a pathogenic variant in MSH6 causing Hereditary Non-Polyposis Colon Cancer phenotype (0.00014), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. To our knowledge, no occurrence of c.3439-26_3439-25delAA in individuals affected with Hereditary Non-Polyposis Colon Cancer and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as benign.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, SCV002552342.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 14, 2023